Lactic acid bacteria are abundantly present in fermented foods such as Kimchi and usually dwell in the digestive tract with a function of degrading fibroid materials and composite proteins into useful metabolites. As such, live microorganisms of a benefit to the host by improving the microbial environment in the gut are collectively designated as probiotics. To function as probiotics, microorganisms must reach the intestine alive after oral uptake and must stay on intestinal surfaces adhered. Therefore, they are fundamentally required to have excellent acid- and bile acid-resistance and ability to adhere to intestinal epithelial cells.
Lactobacillus sp. microorganisms are representative probiotics microorganisms which are abundantly present in Korean conventional fermented foods such as Kimchi. Lactobacillus sp. microorganisms are homo- or hetero-fermentative lactic acid bacilli which can be readily found in gut of animals including a human being or in the fermentation process of diary products or vegetables. Lactobacillus sp. microorganisms are known to have the beneficial functions of vitamin synthesis, anticancer activity and blood cholesterol reduction in addition to maintaining a pH of intestines acidic, inhibiting the excessive growth of harmful bacteria such as E. coli or Clostridium and improving condition of diarrhea and constipation. It has been reported that Acidophilin which is produced by lactic acid bacilli can inhibit the growth of dysentery bacilli, salmonella, staphylococci, E. coli and so on. Further, it can stop diarrhea by suppressing the growth of diarrhea-causing bacteria and normalizing the intestinal microfloral environment (Michael and Philippe, Probiotics and prebiotics: Effects on diarrhea, The journal of nutrition, Volume 137, March 2007, pages 803S-811S; Roberfroid, Prebiotics and probiotics: Are they functional foods?, American journal of clinical nutrition, Volume 71, June 2000, pages 1682S-1687S).
Researches have been intensively made to develop the Lactobacillus sp. microorganisms as probiotic agents and animal feeds by taking advantage of the above properties of Lactobacillus sp. microorganisms. Bacterial diarrhea causes livestock to lose weight or even die. To increase productivity of livestock by preventing the onset of the disease, antibiotics have been generally added to the feedstock of livestock. However, use of antibiotics in animal feeds has been regulated and organic methods of raising livestock have been recommended because of problems such as advent of resistant bacteria and antibiotics residues within livestock products (Korean Patent Laid-Open Publication No. 1998-78358) (McEwen and Fedorka-Cray, Antimicrobial use and resistance in animals, Clinical infectious Diseases, Volume 34, June 2002, pages S93-S106).
In addition, lactic acid bacteria such as Lactobacillus sp. microorganisms are known as exhibiting immunopotentiating activity. Possibly because of worldwide environmental pollution and instant food-uptake increase, allergic and atopic diseases associated with abnormal immunomodulation have increased rapidly over the world including Korea. Recently, an attempt to treat or alleviate diseases by bacteriotherapy in which pathogenic microorganisms are displaced with beneficial bacteria by the oral administration of lactic acid bacteria has been made in Europe. It has been reported that incidence rate of atopic diseases in infants decreased to about half the level by administration of Lactobacillus rhamnosus GG (Kalliomaki et. al., Probiotics in primary prevention of atopic disease: a randomized placebo-controlled trial, Lancet, Volume 357, April 2001, pages 1076-1079) and that area and severity of progressive atopic eczema in children decreased by administration of Lactobacillus rhamnosus and Lactobacillus reuteri (Rosenfeldt et. al., Effect of probiotic Lactobacillus strains in children with atopic dermatitis, Dermatologic and ocular diseases, Volume 111, February 2003, pages 389-395).
The immunopotentiating mechanism of lactic acid bacteria has been steadily studied. Although the underlying mechanism has not been clearly identified, it is generally known that lactic acid affects gastrointestinal tract immune system through oral introduction and existence in the gastrointestinal tract. For example, it has been reported that the uptake of lactic acid bacteria with yogurt increases the antibacterial activity of Peyer's patch's lymphocytes. And, tests with animals and humans showed that lactic acid bacteria potentiate the response of IgA. Further, lactic acid bacteria have an influence on both innate immunity and adaptive immunity. It is known that in innate immunity of the intestinal immune system, lactic acid bacteria defend health against infection by recognizing and killing pathogens. Further, it is known that in adaptive immunity, lactic acid bacteria activate macrophages which functions in phagocytosis of pathogens and presentation of antigens to T lymphocyte, resulting in that production of various cytokines, inter alia, IL12 and IL-18 is increased. In this regard, it is known that some of the constituents of the cell wall of lactic acid bacteria activate the NF-κB and STAT signaling pathway in macrophages and thereby stimulate the production of cytokines. In addition, lactic acid bacteria increase the production of IL-12, IL-18 and TNF-α in dendritic cells, which are specialized antigen-presenting cells abundantly found in the lymph nodes and the mucosa of the digestive tract, as well as the expression of T-lymphocyte-activating surface molecules such as MHC class II and B7-2 (Cross et. al., Anti-allergy properties of fermented foods: an important immunoregulatory mechanism of lactic acid bacteria?, International Immunopharmacology, Volume 1, May 2001, pages 891-901).
T lymphocytes play a central role in adaptive immunity. Adaptive immunity is categorized into a Th1 response leading to cell-mediated immunity and a Th2 response leading to humoral immunity. The cytokines produced by antigen-presenting cells are different between the Th1 response and Th2 response. IL-12, IL-18 and interferon (EFN) are predominantly produced in the Th1 response whereas PGE2, IL-4, and IL-10 are predominantly produced in the Th2 response. For immune system homeostasis, the Th1 and Th2 responses should keep the balance. The disruption of Th1/Th2 balance gives rise to immune disorders. Generally, Th1 cells are more effective against infection, while Th2 cells are responsible mainly for allergic and inflammatory responses. When acting normally, Th2 cells protect the body from dust and other undesired substances. When excessively activated, Th2 cells induce the hyperproduction of IgE antibodies, giving rise to allergic reactions to proteins which are not normally antigenic (e.g., pollen, foods). Therefore, Th1 responses must be in balance with Th2 responses and a surplus or deficiency of either of them causes diseases. Chronic stress induces the continuous release of cortisol, which causes a decrease in Th2 response but an increase in Th1 response, resulting in the induction of cancer, atopy, allergy, and autoimmune diseases (lenkov and Chrousos, Stress hormones, Th1/Th2 patterns, pro/anti-inflammatory cytokines and susceptibility to disease, Trends in Endocrinology and Metabolism, Volume 10, November 1999, pages 359-368).
It is reported that, in vivo, lactic acid bacteria stimulate the production of the Th1 cytokine IFN-γ, but suppress the release of the Th2 cytokines IL-4 and IL-5 in T lymphocytes (Matsuzaki et. al., The effect of oral feeding of Lactobacillus casei strain Shirota on immunoglobulin E production in mice, Journal of Dairy Science, Volume 81, January 1998, pages 48-53). According to another experiment, when ovalbumin-primed mice showing a Th2 bias were administered orally with lactic acid bacteria, the IFN-γ level of the splenocytes increased but the IL-4, IL-5 and IgE levels decreased. Further, the incubation of the splenocytes isolated from ovalbumin-primed mice with a Th2 bias, together with lactic acid bacteria, brought about a change in cytokine and IgE levels in agreement with the results of the oral administration experiment. However, because the incubation of only T lymphocytes together with lactic acid bacteria did not lead to a significant increase in IFN-γ level, it seems that antigen-presenting cells such as macrophages and dendritic cells are required for the IFN-γ production of T lymphocytes (Kato et. al., Lactic acid bacterium potently induces the production of interleukin-12 and interferon-gamma by mouse splenocytes, International Journal of Immunopharmacology, Volume 21, February 1999, pages 121-131). IL-12 and IL-18, both of which are cytokines playing an important role in differentiating Th0 lymphocytes into Th1 lymphocytes, are produced in macrophages or dendritic cells. When treated with lactic acid bacteria in incubation, splenocytes or microphages are known to increase the production of IL-12, IL-18 and IFN-α in dose-dependent manners. As such, lactic acid bacteria increases the production of IL-12, IL-18 and IFN-α in macrophages, thus promoting differentiation into Th1 cells with the concomitant induction of IFN-γ production, so that they can act to drive a Th2-predominant condition toward a Th1/Th2 balance (Cross et. al., Anti-allergy properties of fermented foods: an important immunoregulatory mechanism of lactic acid bacteria?, International Immunopharmacology, Volume 1, May 2001, pages 891-901). Therefore, it is reported that lactic acid bacteria are useful in the prevention or treatment of immune diseases such as cancers, atopy, allergy and autoimmune diseases, which are caused by the disruption of the Th1/Th2 balance triggered by an excessive Th2 response.